The present invention relates generally to peritoneal dialysis and solutions for the same. More specifically, the present invention relates to the use of atrial natriuretic peptide (ANP) as an additive to peritoneal dialysis solutions to increase the adequacy thereof.
Atrial natriuretic peptide (ANP) is a biological hormone. ANP has also been referred to as atrial natriuretic factor (ANF). Its sequence and structure are known and its synthetic equivalent is commercially available in the form of .alpha.-H-ANP. ANP is synthesized primarily in the atrium of the heart as a prehormone that is cleaved to a prohormone of 126 amino acids. The principal circulating form of ANP has been designated as ANP (99-126). The amino terminal (ANP (1-98) fragment is processed into ANP (1-30) and ANP (31-67) fragments, both of which possess biological activity.
ANP has been infused intravenously in treating hypertension, heart disease, acute renal failure and edema. ANP, when infused intravenously, has been shown to increase the glomerular filtration rate (GFR) and filtration fraction. ANP has also been shown to reduce proximal tubule sodium ion concentration and water reabsorption. Further, ANP has been shown to inhibit net sodium ion reabsorption and water reabsorption in the collecting duct, lower plasma renin concentration and inhibit aldosterone secretion. Use of ANP intravenously has also resulted in mean arterial pressure reduction and has led to natriuresis and diuresis.
Dialysis provides a method for supplementing or replacing renal function in certain patients. Principally, hemodialysis and peritoneal dialysis are the two methods that are currently utilized.
In hemodialysis, the patient's blood is passed through an artificial kidney dialysis machine. A membrane in the machine acts as an artificial kidney for cleansing the blood. Because it is an extracorporeal treatment that requires special machinery, hemodialysis is fraught with certain inherent disadvantages such as the availability of dialysis machines and the possibility of infection and contamination.
To overcome the disadvantages associated with hemodialysis, peritoneal dialysis was developed. Peritoneal dialysis utilizes the patient's own peritoneum as a semi-permeable membrane. The peritoneum is a membranous lining of the abdominopelvic walls of the body. The peritoneum is capable of acting as a natural semi-permeable membrane because of its large number of blood vessels and capillaries.
In operation, a peritoneal dialysis solution is introduced into the peritoneal cavity utilizing a catheter. After a sufficient period of time, an exchange of solutes between the dialysate and blood is achieved. Fluid removal is achieved by providing a suitable osmotic gradient from the dialysate to the blood to permit water outflow from the blood. This allows the proper acid-base, electrolyte and fluid balance to be achieved in the blood. After an appropriate dwell period, the dialysis solution or dialysate is drained from the body through a catheter.
While peritoneal dialysis provides some advantages over hemodialysis, primary disadvantages of peritoneal dialysis include an insufficient net ultrafiltration and insufficient clearances of urea nitrogen and sodium. As a result, overall peritoneal dialysis adequacy can be insufficient. Therefore, there is a need for an improved peritoneal dialysis solution which provides a greater net ultrafiltration and increased clearances of components such as urea nitrogen.